Antigen-specific antibodies increase the uptake of antigen, resulting in enhanced T cell activation (Chang, T. W., Immunol. Today, 6:245, 1985). Antibody:antigen immune complexes bind to Fc receptors present on the surface of antigen presenting cells (APC), such as macrophages. These complexes are then internalized and the antigen is processed and presented in the context of MHC-encoded molecules to antigen-specific T cells. Thus, the presence of antigen-specific antibodies can reduce the level of antigen required to activate T cells (Gosselin, E. J., et al., J. Immunol., 149:3477, 1992).
Receptors for the Fc portion of IgG (FcγR) have been characterized at the molecular level. Human monocytes and macrophages express three major classes of FcγR, identified as FcγRI, FcγRII, and FcγRIII. Targeting tetanus toxoid to either FcγRI or FcγRII on monocytes reduces the concentration of antigen required to stimulate T cell proliferation in vitro by a factor of 100-1000 (Kovacsovics-Bakowski, M., et al., Proc. Natl. Acad. Sci. USA, 90:4942, 1993). Therefore, targeting antigen to specific FcγR on APC can dramatically decrease the amount of antigen required to stimulate a specific T cell response.
Following phagocytosis by a monocyte or a macrophage, antigens can be processed and presented to cytolytic T lymphocytes (CTL; Falo, L. D., et al., Nat. Med. 1:649, 1995). It has been shown that mice immunized with an iron particle coupled to a tumor antigen are protected from tumors expressing that tumor antigen (Kovacsovic-Bankowski, M., et al., ibid). Therefore, by inducing monocytes or macrophages to phagocytose tumor antigens, protective immunity to tumors can be induced.